It is well known that many feline and canine companion animals are fussy with their food. An animal will often refuse to eat a foodstuff that it has been eating for some time, or refuse to eat any more than a minimal amount of a foodstuff. Part of this phenomenon can be driven by subtle differences in the sensory profile of the raw materials. These differences might not be perceived by the human consumer, but due to differences in the olfactory and gustatory systems, feline and canine companion animals may well perceive these differences. These sensory differences can be due to natural variation of the raw materials used or when materials are in short supply and have to be substituted with alternatives. This can be very frustrating for the owner and can result in the owner perceiving that the animal is unhappy and not enjoying its food. An animal may also fail to ingest its required amount of essential nutrients if not consuming an adequate amount of food available to it. Therefore, it can clearly be seen that there exists a need for a way to encourage companion animals to eat the foodstuff with which it is provided. Many solutions have been suggested to overcome this problem. Most commercially available pet foods are provided in a range of different flavours and/or textures. However, the companion animal owner will know that often a companion animal will suddenly, for no clear reason, refuse the flavour that the owner perceives to be its most preferred. Much research has been carried out on the flavour preferences of companion animals, by offering them a choice of different foodstuffs.
Taste perception in mammalian animals is governed by the taste receptors found on taste buds of the tongue of the animal and has generally been considered to involve five taste perceptions; salt, sweet, bitter, sour and umami. The taste of a food is determined by which receptors are stimulated. Although some taste receptors share homology between species, the prevalence, frequency and activity of each receptor type depends on the species, since, as would be expected, an herbivorous animal will require different taste stimuli than a carnivorous animal. Feline and canine taste receptors share some homology with those of human, although, as is known, different receptors have different levels of activation and/or preference in feline and canine animals than in humans.
The perception of fat in foods is generally thought to have been due to mouth feel and, to some extent, smell. However, in the human and rodent fields, fatty acid taste receptors have recently been identified (Cartoni et al, 2010; Galindo et al 2012; Martin et al, 2011), indicating that a taste response is also involved in fat perception and detection.
GPR120 (also known as GPR129, 03FAR1, PGR4, FFAR4) is predicted to be a G-protein coupled cell surface receptor, containing seven transmembrane domains (as well as an extracellular portion) involved in the detection of specific fatty acids, and the G-protein associated intracellular portion involved in signal transduction. GPR120 is thought to bind medium to long-chain fatty acids, such as oleic acid and linoleic acid, in their free form. It has been predicted that two isoforms (splice variants) of the GP120 receptor exists in humans, GPR120L and GPR120S, on colonic endocrine cells. It has been suggested that the long isoform does not signal functionally in the perception of taste.
GPR120 is expressed in various mammalian tissue, and has been known to be involved in the stimulation of cholecystokinin (CCK) secretion from STC-1 an intestinal secretory cell line, in addition it has been reported that GPR120 has stimulatory effects on the secretion of glucogon-like peptide (GLP-1). GPR120 is also expressed in the pituitary gland and therefore its potential involvement in stress regulation has also been explored. GPR120 is a known receptor for unsaturated long chain fatty acids and is involved in GLP-1 secretion, insulin sensitisation and anti-inflammatory and anti-obesity effects. It has been suggested that GPR120 agonists or antagonists could be useful as potential therapeutics for the treatment of various metabolic diseases, such as diabetes. However, GPR120 has yet to be explored for its potential palatability enhancing effects.
EP 1688138A1 (Takeda Pharmaceutical Company Limited) is a European patent application directed towards a specific agent for regulating human derived 14273 receptor (GPR120 receptor) function. The document describes low molecular weight synthetic agonists or antagonists for stimulating GPR120. These substances are stated to be useful for the treatment of over-eating, diabetes, or obesity. Alternative agents capable of suppressing GPR120 are described and their use in the treatment of anorexia. The application is limited to human and mouse GPR120 receptors and relates to the identification and use of compounds in a therapeutic context.
Patent application publication WO 2007/134613 (Rheo-Science A/S) relates to GPR120 receptor expression in various mammalian tissues. The application suggests the use of a compound for modulating the expression of GPR120 in order to treat, alleviate, prevent or diagnose diabetes and/or obesity i.e. therapeutic applications in humans.
European patent application EP 1932920A1 (Eisai R&D Management Co Ltd) discloses a method for determining whether a substance alters human GPR120 mediated cell stimulating activity for therapeutic applications.
Patent application publication WO 2011/159297A1 (Metabolex Inc) describes human and rat GPR120 agonists and their use in the treatment of metabolic diseases including diabetes and diseases associated with poor glycaemic control. This application describes that GPR120 agonists were administered to mice to determine the effects on secretion of insulin, glucogon-like peptide 1 and various other hormones. It was shown that GPR120 agonists can lower blood glucose in response to an intra peritoneal glucose challenge in mice.
Bharat Shimpukade et al (Journal of Medicinal Chemistry, Discovery of a Patent and Selective GPR120 Agonist, 2012 May 10; 59(9):4511-4515) disclose a human GPR120 agonist for therapeutic use.
Qi Sun et al (Molecular Pharmacology, Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation, 2010 November; 78(5):804-810) describe human GPR120 agonists for therapeutic purposes.
Takafumi Hara et al (Naunyn-Schmied Arch Pharmacol, Novel Selective Ligands for Free Fatty Acid Receptors GPR120 and GPR40, 2009 September; 380(3):247-255) attempt to identify new therapeutic ligands for human GPR120 receptor. However, the authors were only able to identify partial agonists.
Takayoshi Suzuki et al (Journal of Medicinal Chemistry, Identification of G Protein-Coupled Receptor 120-Selective Agonists Derived from PPARγ Agonists, 2008 Dec. 11; 51(23):7640-7644) describe the need to discover GPR120 selective agonists as they can be used as therapeutic agents.
CD36 (also known a FAT, GP3B, GP4, GPIV, SCARB3, thrombospondin receptor) does not belong to the G-protein coupled receptor family (it belongs to the class B scavenger receptor family), which is unusual with reference to other known fatty acid taste receptors in humans.
Domestic feline animals are known to be fussy with food, and many owners perceive that the cat will only eat certain food stuffs on certain days. Therefore, the ability to ensure that a cat responds well to a particular foodstuff would ensure the consistent acceptance of a foodstuff by an animal, and also to ensure that the owner perceives that the animal is happy and healthy.
Canine animals can also be fussy or in the case of some animals, indiscriminate in food selection. By improving the taste perception of foodstuff, canine animals can be encouraged to eat a particular foodstuff more reliably and consistently.
Currently, cats' and dogs' preference for taste stimuli are identified through feeding tests, which can be inefficient in terms of cost, time and results. Furthermore, the identification of novel taste stimuli is difficult, as many compounds may need to be tested and worked through using animal preference tests, in order to determine which may be reliably attractive to the feline and canine animals. Relatively large amounts of each test compound are necessary for such methods.
Therefore, there is a need for reliable, more efficient screening methods for identifying taste compounds that can bind to and stimulate (or otherwise modulate) certain taste receptors in animals, canine and feline animals in particular.